The pathogenesis of the hypertension in the New Zealand strain of genetically hypertensive (GH) rat is being investigated. Vascular resistance and reactivity to vasopressor agents are being studied in blood- or saline-perfused beds (mesenteric artery, hind limb, tail) in some instances in association with pithing of the rat and stimulation of the sympathetic nervous system via the pithing rod. Increased vascular reactivity is seen in the GH rat, particularly in saline-perfused preparations, apparently because of an alteration in Ca2ion-handling by the vascular smooth muscle cell membrane, and this is being further investigated. In addition, stimulation via the pithing rod has a somewhat greater effect on blood pressure and on hind limb vascular resistance in the GH rat than in normotensive rats. This seems to be due to a humoral substance and further studies are in progress. Finally, 133xenon washout techniques are being used to study renal blood flow distribution in the GH rat. BIBLIOGRAPHIC REFERENCES: Phelan, E. L., Lee, D. R., Wood, A. J. and Simpson, F. O. (1975). The effects of antihypertensive drugs on exchangeable sodium in the New Zealand strain of genetically hypertensive rats. Clin. and exp. Pharmacol. & Physiol. Suppl. 2, 137-140. Wood, A. J., Phelan, E.L. and Simpson, F. O. (1975). Cardiovascular effects of prazosin in normotensive and genetically hypertensive rats. Clin. and exp. Pharmacol. & Physiol. 2, 297-304.